1. Field of the Invention
The invention relates to a novel method for producing [4S-(4alpha, 12aalpha)]-9-amino-4-(dimethylamino) -1,4,4a,5,5a,6,11,12a--octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-nap hthacenecarboxamide, hereinafter called 9-amino-6-demethyl-6-deoxytetracycline, which compound is a valuable intermediate for synthesis of tetracyclines.
2. Description of Prior Art
9-Amino-6-demethyl-6-deoxytetracycline is known and useful as a final product and as an intermediate for the synthesis of substituted tetracyclines [U.S. Pat. No. 3,219,671 and 3,226,436; Journal of the American Chemical Society, 82, 1253(1960)].
Prior to the present invention 9-amino-6-demethyl-6-deoxytetracycline was made by nitrating 6-demethyl-6-deoxytetracycline, followed by catalytic reduction to give the desired product (Boothe, J. H. et al., Journal of the American Chemical Society, 82, 1253 (1960)). This method, however, produces a 1:1.5 mixture of 7- and 9-nitro-6-demethyl-6-deoxytetracyclines which are difficult to separate. When conventional techniques of purification are used, such as crystallization or column chromatography, 9-nitro-6-demethyl-6-deoxotetracycline is obtained in 39% yield. Even these conventional purification techniques, however, do not provide 9-nitro-6-demethyl-6-deoxytetracycline with 100% purity. Some 7-nitro-6-demethyl-6-deoxytetracycline is still present as a contaminant.
The 9-nitro so obtained is then reduced to 9-amino-6-demethyl-6-deoxytetracycline. However, due to the previously described difficulty in separating the 7-nitro-6-demethyl-6-deoxytetracycline from the 9-nitro-6-demethyl-6-deoxytetracycline, some 7-amino-6-demethyl-6-deoxytetracycline is also produced.